SI20327B - Process for producing simvastatin - Google Patents

Process for producing simvastatin Download PDF

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Publication number
SI20327B
SI20327B SI9920024A SI9920024A SI20327B SI 20327 B SI20327 B SI 20327B SI 9920024 A SI9920024 A SI 9920024A SI 9920024 A SI9920024 A SI 9920024A SI 20327 B SI20327 B SI 20327B
Authority
SI
Slovenia
Prior art keywords
formula
diol lactone
preparation
simvastatin
inorganic base
Prior art date
Application number
SI9920024A
Other languages
Slovenian (sl)
Other versions
SI20327A (en
Inventor
Naoaki Taoka
Kenji Inoue
Original Assignee
Kaneka Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kaneka Corporation filed Critical Kaneka Corporation
Publication of SI20327A publication Critical patent/SI20327A/en
Publication of SI20327B publication Critical patent/SI20327B/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/30—Oxygen atoms, e.g. delta-lactones
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyrane Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A convenient, efficient and industrially favorable process for producing simvastatin which is useful as an HMG-coA reductase inhibitor. This process comprises deacylating lovastatin by treating with an inorganic base and a secondary or tertiary alcohol to thereby form diol lactone, and then selectively protecting, acylating, deblocking and lactonizing the diol lactone by using a ketal or acetal protective group to thereby give simvastatin.

Claims (4)

1 Patentni zahtevki 1. Postopek za pripravo diolnega laktona s formulo (3) HA process for the preparation of a diol lactone of formula (3) H OOh označen s tem, da obsega obdelovanje lovastatina s formulo (1) z anorgansko bazo^in sekundarnim ali terciarnim alkoholom, da nastane triolna kislina s formulo (2)characterized in that it comprises treating lovastatin of formula (1) with an inorganic base ^ and a secondary or tertiary alcohol to form a triolic acid of formula (2) ί in zaporedno nakisanje in laktoniziranje triolne kisline (2), da nastane diolni lakton (3)·ί and successive acidification and lactonization of triolic acid (2) to form diol lactone (3) · 2. Postopek za pripravo diolnega laktona s formulo (3) po zahtevku 1, označen s tem, daje sekundami ali terciarni alkohol i-propanol ali t-butanol.Process for the preparation of a diol lactone of formula (3) according to Claim 1, characterized in that the seconds are either tertiary alcohol i-propanol or t-butanol. 3. Postopek za pripravo diolnega laktona s formulo (3) po zahtevku 1 ali 2, označen s tem, daje anorganska baza hidroksid alkalijske kovine ali alkoksid alkalijske kovine.Process for the preparation of a diol lactone of formula (3) according to Claim 1 or 2, characterized in that the inorganic base is an alkali metal hydroxide or an alkali metal alkoxide. 4. Postopek za pripravo diolnega laktona s formulo (3) po zahtevku 3, označen s tem, da je hidroksid alkalijske kovine litijev hidroksid, natrijev hidroksid ali kalijev hidroksid.Process for the preparation of a diol lactone of formula (3) according to Claim 3, characterized in that the alkali metal hydroxide is lithium hydroxide, sodium hydroxide or potassium hydroxide.
SI9920024A 1998-12-10 1999-12-10 Process for producing simvastatin SI20327B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP35186598 1998-12-10
PCT/JP1999/006929 WO2000034264A1 (en) 1998-12-10 1999-12-10 Process for producing simvastatin

Publications (2)

Publication Number Publication Date
SI20327A SI20327A (en) 2001-02-28
SI20327B true SI20327B (en) 2015-02-27

Family

ID=18420148

Family Applications (1)

Application Number Title Priority Date Filing Date
SI9920024A SI20327B (en) 1998-12-10 1999-12-10 Process for producing simvastatin

Country Status (14)

Country Link
US (1) US6331641B1 (en)
EP (2) EP1055671B1 (en)
JP (2) JP4440476B2 (en)
KR (1) KR100672269B1 (en)
CN (2) CN1122029C (en)
AT (1) ATE283849T1 (en)
AU (1) AU1683000A (en)
CA (1) CA2320163C (en)
CZ (2) CZ299522B6 (en)
DE (1) DE69922348T2 (en)
ES (1) ES2234323T3 (en)
HU (1) HUP0103021A3 (en)
SI (1) SI20327B (en)
WO (1) WO2000034264A1 (en)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6573392B1 (en) 1999-11-11 2003-06-03 Biocon India Limited Process for manufacturing simvastatin and the novel intermediates
US6573385B1 (en) 1999-11-11 2003-06-03 Biocon India Limited Process for manufacturing simvastatin and novel intermediates thereof
GB0011120D0 (en) 2000-05-09 2000-06-28 Avecia Ltd Process
KR100361833B1 (en) * 2000-06-20 2002-11-22 주식회사 엘지생명과학 Process for manufacturing simvastatin
NL1015744C2 (en) 2000-07-19 2002-01-22 Dsm Nv Process for the preparation of 2- (6-substituted-1,3-dioxan-4-yl) acetic acid derivatives.
BR0211072A (en) 2001-07-13 2004-12-14 Astrazeneca Uk Ltd Process for preparing a compound, compound, and method for preparing a compound
KR100435142B1 (en) * 2002-01-09 2004-06-09 한미약품 주식회사 Improved process for the preparation of simvastatin
KR100502833B1 (en) * 2002-03-25 2005-07-25 보령제약 주식회사 Improved preparation method of simvastatin and their intermediates
KR100502834B1 (en) * 2002-03-25 2005-07-20 보령제약 주식회사 The preparation method of simvastatin by improved process of lactonization and its purification process
US6603022B1 (en) 2002-05-10 2003-08-05 Biocon India Limited Process for manufacturing Simvastatin and novel intermediates thereof
EP1375493A1 (en) * 2002-06-17 2004-01-02 Dsm N.V. Process for the preparation of an dioxane acetic acid ester
GB0218781D0 (en) * 2002-08-13 2002-09-18 Astrazeneca Ab Chemical process
GB0312896D0 (en) 2003-06-05 2003-07-09 Astrazeneca Ab Chemical process
UY28501A1 (en) * 2003-09-10 2005-04-29 Astrazeneca Uk Ltd CHEMICAL COMPOUNDS
AU2004284068B2 (en) * 2003-10-21 2011-06-02 Verenium Corporation Methods for making simvastatin and intermediates
GB0324791D0 (en) 2003-10-24 2003-11-26 Astrazeneca Ab Chemical process
WO2005058861A1 (en) * 2003-12-16 2005-06-30 Uk Chemipharm Co., Ltd. Process for preparing simvastatin.
CN1754870A (en) * 2004-09-30 2006-04-05 淮北市辉克药业有限公司 Process for the preparation of simvastatin
GB0428328D0 (en) * 2004-12-24 2005-02-02 Astrazeneca Uk Ltd Chemical process
GB0514078D0 (en) * 2005-07-08 2005-08-17 Astrazeneca Uk Ltd Chemical process
US20110059493A1 (en) * 2007-08-27 2011-03-10 Brian Morgan Methods for Making Simvastatin and Intermediates
JP2009114121A (en) * 2007-11-06 2009-05-28 Kaneka Corp Method for producing simvastatin
CN101575328B (en) * 2008-05-09 2012-07-04 上海医药工业研究院 Synthesizing method of simvastatin intermediate
CN102690254B (en) * 2008-05-09 2014-06-04 上海医药工业研究院 Simvastatin ammonium salt intermediates and preparation methods thereof
CN110483459A (en) * 2019-09-10 2019-11-22 山东罗欣药业集团恒欣药业有限公司 A kind of synthetic method of Simvastatin
CN110563680A (en) * 2019-09-10 2019-12-13 山东罗欣药业集团恒欣药业有限公司 Preparation method of medicine for treating hyperlipemia

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ZA81703B (en) * 1980-02-04 1982-09-29 Merck & Co Inc New antihypercholesterolemic compounds,intermediates and processes
US4444784A (en) * 1980-08-05 1984-04-24 Merck & Co., Inc. Antihypercholesterolemic compounds
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Also Published As

Publication number Publication date
KR100672269B1 (en) 2007-01-23
WO2000034264A1 (en) 2000-06-15
CN1290261A (en) 2001-04-04
CZ299566B6 (en) 2008-09-03
CN1493570A (en) 2004-05-05
EP1055671A1 (en) 2000-11-29
JP2009185041A (en) 2009-08-20
EP1533308A3 (en) 2005-09-14
ATE283849T1 (en) 2004-12-15
US6331641B1 (en) 2001-12-18
AU1683000A (en) 2000-06-26
EP1055671B1 (en) 2004-12-01
DE69922348D1 (en) 2005-01-05
CN1226296C (en) 2005-11-09
ES2234323T3 (en) 2005-06-16
CN1122029C (en) 2003-09-24
EP1533308A2 (en) 2005-05-25
KR20010040760A (en) 2001-05-15
JP5048709B2 (en) 2012-10-17
CA2320163C (en) 2008-09-23
DE69922348T2 (en) 2005-12-01
SI20327A (en) 2001-02-28
EP1533308B1 (en) 2014-01-15
JP4440476B2 (en) 2010-03-24
CA2320163A1 (en) 2000-06-15
HUP0103021A3 (en) 2002-04-29
HUP0103021A2 (en) 2001-12-28
CZ20003149A3 (en) 2000-12-13
CZ299522B6 (en) 2008-08-27
EP1055671A4 (en) 2002-05-08

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Legal Events

Date Code Title Description
IF Valid on the event date
SP73 Change of data on owner

Owner name: KANEKA CORPORATION; JP

Effective date: 20081010

OU02 Decision according to article 73(2) ipa 1992, publication of decision on partial fulfilment of the invention and change of patent claims

Effective date: 20150109